The primary goal of this program project is to determine the properties of vascular smooth muscle (VSM) that regulate its contractile state, and hence blood flow, under physiological conditions and in hypertension. Since numerous factors may play a role in altering VSM contractility, and since so little is known about this important tissue a multifaceted study will be undertaken involving 13 faculty members who represent the Departments of Biochemistry, Pharmacology and Physiology. The 11 projects deal with the mechanics of the contractile system, the metabolism, the electrophysiology and the pharmacology of VSM. The projects are entitled: "Mechanics and reactivity of microvessesl," "The contractile system of VSM," "Mechanisms of control of small vessel tone: role of endogenous metabolites," "Cyclic nucleotide metabolism in VSM cell cultures," "Lactate transport in VSM; normal vs. diabetis," "Regulation of energy metabolism and protein turnover in VSM," "Modulation of VSM membrane fluidity by serUm lipoproteins," "Relationship of aorta microsomal membrane properties, hypertension and dietary lipid components in the SHR," "Electrophysiology of VSM," "Norepinephrine release and reactivity of VSM," "Altered tissue reactivity to angiotensin". The various projects are closely related so that there is considerable interaction among the participants. The experiments include whole animal studies, isolated tissues and organs, VSM cell cultures and subcelluar fractions, and core facilities (4) are provided to meet the experimental needs of the investigators. They consist of a VSM cell culture facility, an electron microscopy unit and a colony of spontaneous hypertensive rats (SHR) and suitable controls (WKY). In addition, an administrative core facility oversees the day-by-day operation of the grant. The information to be gained from this program project will not only provide necessary basic data on the mechanisms involved in the function of VSM but may well lead to more rational approaches for the treatment of disease caused by abnormally functioning VSM.